appropriate target, attempt preliminary
optostimulation to determine whether the
cell is responsive. Assuming it is, the system
could then perform a pre-programmed ex-
periment. If it’s not, it would continue to
scan for another likely candidate, repeating the process until either it has collected a predetermined number of cells, or all
cells in the sample have been judged to be
overgrown or nonresponsive.

During a five-day practical course called
Non-Neuronal Optogenetics: From Design
to Application in Cell Signaling and Tissue
Morphogenesis, given at the European
Molecular Biology Lab in June 2016,
Dr. Valentina Emiliani of the European
Neuroscience Institute (Paris, France) pre-
sented the work of her wavefront-engineer-
ing microscopy team, which is developing
optical techniques based on spatiotempo-
ral engineering of optical wavefronts using
phase modulation. The approach promises to minimize power losses, quickly adapt
excitation patterns to an experiment, and
enable 3D sculpting of excitation volumes.

Toward clinical application

Commenting on recently reported research
done at Princeton, Toettcher’s colleague,
assistant professor of chemical and biologi-
cal engineering Clifford Brangwynne, says,
“This is fundamental science we’re doing, answering basic questions about phase
transitions in cells.” The ultimate goal,
however, is larger: “we’re hoping these
insights will reveal not only how healthy
cells work, but also how they can become
diseased, and maybe eventually cured.” 5
Indeed, many applications that promise
clinical value beyond the brain are emerging (see frontis, page 41).

So far, the optogenetics-based work thathas made the greatest progress toward clin-ical application is RST-001, an agent de-signed by Wayne State University (Detroit,MI) researcher Zhuo-Hua Pan (who mayin fact be the originator of the optogeneticstechnique, according to a September 2016article in STAT, a Boston Globe Mediapublication) for treatment of retinitis pig-mentosa (RP). After securing a patent touse channelrhodopsin- 2 for vision resto-ration, Pan licensed it to a company calledRetroSense Therapeutics (Ann Arbor, MI),which was acquired by global pharmaceu-tical company Allergan in late 2016 in anall-cash transaction starting with a $60million upfront payment, and involvingpotential regulatory and commercializa-tion milestone payments.

RST-001 creates new photosensors inretinal ganglion cells: The FDA clearedRetroSense’s Investigational New Drug(IND) application in August 2015, andthe company reported success with aPhase I/IIa clinical trial to evaluate RST-001’s safety a year later. Allergan chiefresearch and development officer DavidNicholson said in a statement, “The RST-001 program and its optogenetic genetherapy approach could be a real break-through in the treatment of unmet needsacross a host of retinal conditions, includ-ing RP,” adding that “Allergan is excit-ed by the prospect of advancing an en-tirely new approach.”Another example of the potential forclinical application of non-neuronal op-togenetics is detailed in a paper titled, “ASynthetic Erectile Optogenetic StimulatorEnabling Blue-Light-Inducible PenileErection.” 6

Even if non-neural efforts account for
only a minority of work being done in
the roughly 1000 laboratories world-
wide doing optogenetic research (ac-
cording to Credence Research’s study,
“Optogenetics Market Growth, Future
Prospects and Competitive Analysis,
2016-2022”), the field has an interesting future.